反应详情

To a cooled (ice bath) solution of (4S,6S)-4-(5-amino-2,3-difluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (0.095 g, 0.307 mmol) and 5-cyano-2-pyridinecarboxylic acid (0.055 g, 0.369 mmol) in THF (2.5 mL) and MeOH (1.5 mL) was added 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (0.118 g, 0.399 mmol). After stirring for 30 min, the ice bath was removed. The reaction was stirred at ambient temperature for 15 h. The reaction was quenched with saturated sodium bicarbonate solution. MeOH was removed by rotary evaporation. The aqueous residue was extracted with EtOAc (2×). The organic extracts were combined, concentrated and purified by Shimadzu HPLC to afford N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4,5-difluorophenyl)-5-cyanopicolinamide (0.053 g, 0.121 mmol, 39.3% yield) as white solid. MS m/z=440.1 [M+H]+. Calculated for C19H14F5N5O2: 439.3

1. customthe ice bath was removed
2. stirringThe reaction was stirred at ambient temperature for 15 h
3. customThe reaction was quenched with saturated sodium bicarbonate solution
4. customMeOH was removed by rotary evaporation
5. extractionThe aqueous residue was extracted with EtOAc (2×)
6. concentrationconcentrated
7. custompurified by Shimadzu HPLC